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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #345553

Research Project: Rational Design of a Broadly Protective Live Attenuated Influenza A Virus Vaccine (LAIV) for use in Swine

Location: Virus and Prion Research

Title: Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza vaccine protects from homologous challenge

item KAPLAN, BRYAN - Orise Fellow
item SOUZA, CARINE - Orise Fellow
item GAUGER, PHILLIP - Iowa State University
item STAUFT, CHARLES - Codagenix, Inc
item COLEMAN, J - Codagenix, Inc
item MUELLER, STEFFEN - Codagenix, Inc
item Vincent, Amy

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2018
Publication Date: 2/14/2018
Citation: Kaplan, B.S., Souza, C.K., Gauger, P.C., Stauft, C.B., Coleman, J.R., Mueller, S., Vincent, A.L. 2018. Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza vaccine protects from homologous challenge. Vaccine. 36(8):1101-1107. https://doi.10.1016/j.vaccine.2018.01.027.

Interpretive Summary: Influenza A viruses (IAV) in swine constitutes a major economic burden for producers. Current IAV vaccines used in swine are marginally effective at preventing disease and do not provide cross-protective immunity to the vast diversity of IAV circulating in pig herds in the United States. Here we report the evaluation of a codon-pair bias de-optimized (CPBD) live attenuated influenza vaccine (LAIV) in pigs. CPBD introduces changes into the viral genome that reduce virus replication, attenuating the virus. Previous studies have shown CPBD LAIV capable of protecting mice and ferrets from IAV infection. Pigs inoculated with CPBD LAIV displayed no outward clinical disease or detectable lung pathology, proving CPBD viruses are attenuated in pigs. Further, we detected high titers of antibodies in the blood following vaccination indicating CPBD viruses can induce a strong immune response. Vaccinated pigs were then inoculated with IAV and virus was not detected. These results show CPBD LAIV to provide protection in pigs warranting further development for use in swine.

Technical Abstract: Influenza A virus (IAV) in swine constitutes a major economic burden for producers as well as a potential threat to public health. Whole inactivated virus vaccines (WIV) are the predominant countermeasure employed to control IAV in swine herds in the United States despite the superior protection, and diminished adverse effects, induced by live attenuated influenza vaccines (LAIV). A major hurdle for the development of LAIV exists in achieving the proper level of attenuation while maintaining immunogenicity. Using Synthetic Attenuated Virus Engineering (SAVE) to introduce codon-pair bias de-optimization (CPBD) into the hemagglutinin (HA) and neuraminidase (NA) gene segments of pandemic H1N1 IAV, a novel LAIV was produced and evaluated for attenuation, immunogenicity, and efficacy in pigs. The CPBD LAIV induced inappreciable pathology following intranasal administration yet induced robust serum and mucosal antibody titers. CPBD LAIV vaccinated pigs challenged with wild-type virus showed sterilizing immunity, highlighted by the absence of detectable virus titers in the nasal passages and lungs. These results demonstrate the efficacy of a LAIV designed by SAVE codon de-optimization in pigs, providing support for the continued development of CPBD LAIV for use in swine.